Bioelectric Dysregulation in Cancer Initiation, Promotion, and Progression.

Maulee Sheth,Leyla Esfandiari

doi:10.3389/fonc.2022.846917

Abstract

Cancer is primarily a disease of dysregulation – both at the genetic level and at the tissue organization level. One way that tissue organization is dysregulated is by changes in the bioelectric regulation of cell signaling pathways. At the basis of bioelectricity lies the cellular membrane potential or Vmem, an intrinsic property associated with any cell. The bioelectric state of cancer cells is different from that of healthy cells, causing a disruption in the cellular signaling pathways. This disruption or dysregulation affects all three processes of carcinogenesis – initiation, promotion, and progression. Another mechanism that facilitates the homeostasis of cell signaling pathways is the production of extracellular vesicles (EVs) by cells. EVs also play a role in carcinogenesis by mediating cellular communication within the tumor microenvironment (TME). Furthermore, the production and release of EVs is altered in cancer. To this end, the change in cell electrical state and in EV production are responsible for the bioelectric dysregulation which occurs during cancer. This paper reviews the bioelectric dysregulation associated with carcinogenesis, including the TME and metastasis. We also look at the major ion channels associated with cancer and current technologies and tools used to detect and manipulate bioelectric properties of cells.

Highlights

Carcinogenesis, termed oncogenesis or tumorigenesis, is rooted in two major theories or hypotheses, both significantly different from one another
The somatic mutation theory (SMT), which has been prevailing in cancer research for more than sixty years proposes that the origin of cancer can be explained by an accumulation of several DNA mutations in a single somatic cell
The tissue organization field theory (TOFT) proposed in 1999, hypothesizes that carcinogenesis is a problem of tissue organization instead of having a cellular level origin

Summary

Introduction

Carcinogenesis, termed oncogenesis or tumorigenesis, is rooted in two major theories or hypotheses, both significantly different from one another. The production of EVs is aberrant during cancer which in turn plays an important role in disturbing the bioelectrical signaling pathways between cells. We provide a more extensive review of bioelectric regulation in multiple cancer processes including initiation, promotion, the tumor microenvironment, and metastasis.

Results

Conclusion